Interpretive Summary: Preweaning piglet loss approaches $1.6 billion/year (2005) which is a major economic burden to the swine industry. A contributing factor to this loss is intrauterine growth retardation (IUGR) of the fetus that can lead to prenatal death or failure of the piglet to thrive postnatally. A strong correlation exists between placental and fetal weight once a critical placental weight threshold is crossed. However, little is known about the molecular etiology of this pathology, particularly in swine. This study examined the expression of messenger RNA (mRNA) for 14 genes regulating important placental functions or known to be altered in the placenta of IUGR offspring at the completion of placentation. Only endothelial nitric oxide synthase, exhibited a change in expression. Endothelial nitric oxide synthase mRNA was increased in the IUGR whole placental tissue and specialized placental structures regulating uterine-derived nutrient uptake compared to age-matched controls. A comparison with whole placental tissue of controls from an earlier developmental stage suggested that the down-regulation of endothelial nitric oxide synthase seen in age-matched control placentas may be blocked in IUGR placenta. Physiologically, endothelial nitric oxide synthase plays an indirect but important role in control of vascular tone by promoting blood vessel dilation to increase blood flow. Inadequate nutrition is thought to play an important role the retarded growth of the IUGR fetus, therefore the increase of endothelial nitric oxide synthase in IUGR placentas may be a compensatory mechanism to boost nutritional support to the IUGR fetus and its survival.

Technical Abstract:
The onset of intrauterine growth retardation (IUGR) hinders fetal growth during gestation and is strongly correlated to a placental weight that has declined below critical threshold. However, little is known about the molecular etiology of this pathology, particularly in swine. In this study, the expression of candidate genes associated with placental development or known to be altered with IUGR was examined in the pig placenta. Total RNA was isolated from whole placental tissue and specialized placental structures, areolae, from control and IUGR fetuses at gestational day 50 and control placentas at gestational day 37. The mRNA was reverse transcribed and candidate genes were amplified by real-time PCR to evaluate the relative quantity of each transcript. Endothelial nitric oxide synthase was the only gene found to be differentially expressed between control and IUGR fetuses at gestational day 50. When comparing different stages of placental development, endothelial nitric oxide synthase, endoglin, and transforming growth factor ß were up-regulated and insulin-like growth factor 2 was down-regulated at gestational day 37 compared to gestational day 50. Of note was evidence that the elevated level of endothelial nitric oxide synthase seen earlier in gestation appeared to remain within the IUGR placenta. The importance of endothelial nitric oxide in modulating vascular tone may indicate that in the IUGR placenta, alterations in blood flow may be more essential for the maintenance of pregnancy than the differentiation or growth potential of the placental cell subtypes.